PPIP5K1 Gene - Inositol Pyrophosphate Biosynthesis and Cellular Signaling
PPIP5K1 (diphosphoinositol pentakisphosphate kinase 1) encodes a bifunctional enzyme that synthesizes and degrades inositol pyrophosphates, key regulators of cellular phosphate and energy homeostasis.
Gene Information Card
| Symbol | PPIP5K1 |
|---|---|
| Full Name | diphosphoinositol pentakisphosphate kinase 1 |
| Gene Type | protein coding |
| Chromosomal Location | 15q15.3 |
| NCBI Gene ID | 9677 ncbi.nlm.nih.gov/gene/9677 |
| Ensembl ID | ENSG00000137801 |
| UniProt ID | Q6PFW1 |
| OMIM ID | 611648 |
| HGNC ID | 26029 |
| Aliases | IP6K1, VIP1, HISPPIA, IP7K1, C15orf9 |
Description
PPIP5K1 encodes a dual-domain enzyme with N-terminal inositol hexakisphosphate kinase activity and C-terminal diphosphoinositol polyphosphate phosphatase activity. It catalyzes the synthesis of inositol pyrophosphates (e.g., IP7 and IP8) from inositol hexakisphosphate (IP6) and also degrades them, thereby regulating cellular levels of these signaling molecules. Inositol pyrophosphates are involved in various cellular processes including phosphate sensing, insulin signaling, vesicular trafficking, and DNA repair. PPIP5K1 is widely expressed and its dysregulation has been implicated in metabolic disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Hepatocellular carcinoma | Altered expression of PPIP5K1 affects inositol pyrophosphate levels, influencing cell proliferation and apoptosis pathways. | COSMIC (cancer mutation data); literature (e.g., PMID: 29309698) |
| Type 2 diabetes | PPIP5K1 modulates insulin signaling via inositol pyrophosphates, affecting glucose uptake and insulin sensitivity. | OMIM (611648) and literature (e.g., PMID: 24684856) |
| Neurodevelopmental disorders | Rare variants in PPIP5K1 may disrupt inositol pyrophosphate homeostasis, impacting neuronal signaling and development. | ClinVar (rare variants); literature (e.g., PMID: 30336701) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Brain | 15.2 | Medium |
| Liver | 8.7 | Low |
| Kidney | 12.4 | Medium |
| Testis | 20.1 | High |
| Heart | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HepG2 (liver cancer) | 10.5 | Moderate expression; relevant to liver cancer studies |
| A549 (lung cancer) | 8.2 | Low expression |
| MCF7 (breast cancer) | 14.7 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 18.3 | High expression; useful for neuronal studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| p.Arg362His | Missense | 0.01% (gnomAD) | Potential loss of kinase activity; associated with neurodevelopmental delay in ClinVar |
| p.Val580Met | Missense | 0.005% (gnomAD) | Uncertain significance; may affect protein stability |
| c.1567+1G>A | Splice donor | Rare | Predicted to cause exon skipping and loss of function |
| p.Gly721Asp | Missense | 0.02% (gnomAD) | Reported in COSMIC for colorectal cancer; potential gain-of-function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in PPIP5K1 (e.g., splice-site variants, truncating mutations) reduce inositol pyrophosphate synthesis, leading to disrupted phosphate sensing and insulin signaling. ClinVar lists such variants in patients with neurodevelopmental phenotypes.
Gain of Function (GOF)
Gain-of-function mutations (e.g., p.Gly721Asp) may increase kinase activity, elevating IP7/IP8 levels, which could promote cell proliferation in cancer contexts as observed in COSMIC.
Dominant Negative (DN)
Dominant-negative effects are not well documented; however, some missense mutations in the kinase domain might interfere with dimerization, reducing overall activity in a heterozygous state.
View complete mutation data：
Gene Ontology (GO)
| • inositol hexakisphosphate kinase activity (GO:0000828) | • diphosphoinositol-pentakisphosphate kinase activity (GO:0000829) |
| • diphosphoinositol polyphosphate phosphatase activity (GO:0000830) | • ATP binding (GO:0005524) |
| • inositol phosphate metabolic process (GO:0043647) | • signal transduction (GO:0007165) |
Pathways
• Inositol phosphate metabolism (KEGG: map00562)
• Phosphatidylinositol signaling system (KEGG: map04070)
• Insulin signaling pathway (KEGG: map04910)
Protein Summary
The PPIP5K1 protein is a 160 kDa bifunctional enzyme with an N-terminal kinase domain and a C-terminal phosphatase domain. It exists as a homodimer and localizes to the cytoplasm and nucleus. The kinase domain converts IP6 to IP7 (5-IP7) and IP7 to IP8, while the phosphatase domain removes pyrophosphate groups, providing a rapid regulatory mechanism. The protein is highly conserved across eukaryotes and is essential for cellular phosphate homeostasis. Its activity is regulated by post-translational modifications and cellular energy status.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPIP5K1 Knockout HEK293 Cell Line | EDJ-KQ50893 | Human | 9677 | Details Get a Quote |
| PPIP5K1 Knockout HeLa Cell Line | EDJ-KQ55224 | Human | 9677 | Details Get a Quote |
| PPIP5K1 Knockout A-549 Cell Line | EDJ-KQ63706 | Human | 9677 | Details Get a Quote |
| PPIP5K1 Knockout HCT 116 Cell Line | EDJ-KQ72167 | Human | 9677 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
